We made tremendous progress on our aims related to this project. We began the grant period having never worked with human embryonic stem cells (hESCs). We ended the project period having published 3 scientific papers in high profile journals (PNAS, Cell Stem Cell, Stem Cells) covering various aspects of this work as outlined in the grant. In addition, at least two more papers will be published in the next year related to this work.
To summarize the work, we employed hESCs to model the development of pluripotent cells from undifferentiated “embryonic-like” cells to neural stem cells to neuronal progenitors to committed neurons and finally to fully active mature neurons. Furthermore, we developed methods to purify these cells at each step in order to determine their gene expression profile. We have made fascinating observations of changes in gene expression in these cells as they go from embryonic to fully mature neurons. The simplest way to describe this method is that we have modeled the development of a human tissue in vitro, which, without the use of hESCs would normally be impossible. As a result, we now know more about how these cells development than ever before. With this knowledge in hand, we can now test hypotheses about how neurons develop in the embryo in vitro.
How will these results be applied in the future? Because we now have a basic framework by which human motor neurons develop in vitro, we can attempt to affect this process by boosting or ablating expression of those genes that are induced during maturation. This will tells us which genes play a functional role in this process and perhaps hint towards future therapies for motor neuron diseases.